In:
The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 154.3-154.3
Abstract:
Aging is associated with chronic inflammation and increased risk for degenerative disorders and diseases. In the elderly there is a development of insulin resistance, increased visceral adiposity and dysfunctional adipose tissue (AT) homeostasis; however the mechanisms of age-induced immune defects in AT is unclear. AT contains numerous immune populations, which play well-known roles in regulating both inflammatory responses and metabolic homeostasis. Our prior studies have identified that the canonical inflammasome, NLRP3, is required for diet-induced AT inflammation and age-related inflammation in multiple organs. We hypothesized that NLRP3 is required for age-induced changes in AT immune cells and that deficiency in Nlrp3 will improve AT function during aging. Here we show that unlike obesity, aging is associated with reduction in specific AT macrophages subsets. Whole transcriptome sequencing of AT macrophages from aged mice revealed increased caspase-1 activation and distinct signatures that were regulated in part by Nlrp3. Linear support vector regression and bioinformatics analyses revealed that AT macrophages do not display classical M1–M2 like transcriptome and display AT-specific signatures that are distinct from other tissue macrophages in gut, brain, liver and spleen. We identified that as compared to 24-month old WT, the aged Nlrp3−/− animals were protected from alterations in AT macrophage activation. Furthermore, Nlrp3-mediated reduction in AT inflammation and macrophage activation led to protection from age-related defects in AT function. Overall our findings suggest that NLRP3-dependent immune-metabolic interactions within AT contribute to age-related inflammation and metabolic dysfunction.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.198.Supp.154.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2017
detail.hit.zdb_id:
1475085-5
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